PCA-based bootstrap confidence interval tests for gene-disease association involving multiple SNPs.

BACKGROUND: Genetic association study is currently the primary vehicle for identification and characterization of disease-predisposing variant(s) which usually involves multiple single-nucleotide polymorphisms (SNPs) available. However, SNP-wise association tests raise concerns over multiple testing. Haplotype-based methods have the advantage of being able to account for correlations between neighbouring SNPs, yet assuming Hardy-Weinberg equilibrium (HWE) and potentially large number degrees of freedom can harm its statistical power and robustness. Approaches based on principal component analysis (PCA) are preferable in this regard but their performance varies with methods of extracting principal components (PCs). RESULTS: PCA-based bootstrap confidence interval test (PCA-BCIT), which directly uses the PC scores to assess gene-disease association, was developed and evaluated for three ways of extracting PCs, i.e., cases only(CAES), controls only(COES) and cases and controls combined(CES). Extraction of PCs with COES is preferred to that with CAES and CES. Performance of the test was examined via simulations as well as analyses on data of rheumatoid arthritis and heroin addiction, which maintains nominal level under null hypothesis and showed comparable performance with permutation test. CONCLUSIONS: PCA-BCIT is a valid and powerful method for assessing gene-disease association involving multiple SNPs.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Chemical composition and anti-arthritic activity of the essential oil from Litsea cubeba against Type II collagen rheumatoid arthritis in rat collagen

Purpose: To study the curative effect of the volatile oil from Litsea cubeba (EOL) on type II collagen (CII) induced arthritic (CIA) rat. Methods: The chemical constituents of EOL were analyzed by gas chromatography-mass spectrometry (GC-MS). The analgesic effect of the oil was assessed by acetic acid-stimulated torsion and hot plate methods, while antiinflammatory potential was further assessed by in an ear oedema model induced by dimethylbenzene in mice. The anti-rheumatoid arthritis (RA) activity of EOL in mice was evaluated in terms of paw volume, arthritis index, thymus and spleen index, and serum inflammatory factor levels. Results: GC-MS showed that α-citral (26.42 %), β-citral (21.94 %), and limonene (12.79 %) were the main components of EOL. Different doses of EOL (50, 100, 200 mg/kg) exerted varying inhibitory effects on torsion in mice induced by acetic acid (p < 0.01) but had no significant effect on thermal stimulation-induced pain. EOL reduced ear oedema in mice (p < 0.01). In addition, EOL (50, 100, 200 mg/kg) reduced the mouse paw volume, arthritis index, and thymus and spleen index (p < 0.01). Furthermore, EOL reduced proinflammatory cytokines in serum but increased antiinflammatory cytokines (p < 0.01). Conclusion: EOL ameliorates symptoms of inflammation in CIA rats by inhibiting inflammatory reactions, suggesting it could be further developed as an anti-arthritic drug. Keywords: Litsea cubeba, Essential oil, Rrheumatoid arthritis, Pro-inflammatory cytokine

Effects of fatty acid activation on photosynthetic production of fatty acid-based biofuels in Synechocystis sp. PCC6803

<p>Abstract</p> <p>Background</p> <p>Direct conversion of solar energy and carbon dioxide to drop in fuel molecules in a single biological system can be achieved from fatty acid-based biofuels such as fatty alcohols and alkanes. These molecules have similar properties to fossil fuels but can be produced by photosynthetic cyanobacteria.</p> <p>Results</p> <p><it>Synechocystis </it>sp. PCC6803 mutant strains containing either overexpression or deletion of the <it>slr1609 </it>gene, which encodes an acyl-ACP synthetase (AAS), have been constructed. The complete segregation and deletion in all mutant strains was confirmed by PCR analysis. Blocking fatty acid activation by deleting <it>slr1609 </it>gene in wild-type <it>Synechocystis </it>sp. PCC6803 led to a doubling of the amount of free fatty acids and a decrease of alkane production by up to 90 percent. Overexpression of <it>slr1609 </it>gene in the wild-type <it>Synechocystis </it>sp. PCC6803 had no effect on the production of either free fatty acids or alkanes. Overexpression or deletion of <it>slr1609 </it>gene in the <it>Synechocystis </it>sp. PCC6803 mutant strain with the capability of making fatty alcohols by genetically introducing fatty acyl-CoA reductase respectively enhanced or reduced fatty alcohol production by 60 percent.</p> <p>Conclusions</p> <p>Fatty acid activation functionalized by the <it>slr1609 </it>gene is metabolically crucial for biosynthesis of fatty acid derivatives in <it>Synechocystis </it>sp. PCC6803. It is necessary but not sufficient for efficient production of alkanes. Fatty alcohol production can be significantly improved by the overexpression of <it>slr1609 </it>gene.</p

A Simple Graphene NH₃ Gas Sensor via Laser Direct Writing.

Ammonia gas sensors are very essential in many industries and everyday life. However, their complicated fabrication process, severe environmental fabrication requirements and desorption of residual ammonia molecules result in high cost and hinder their market acceptance. Here, laser direct writing is used to fabricate three parallel porous 3D graphene lines on a polyimide (PI) tape to simply construct an ammonia gas sensor. The middle one works as an ammonia sensing element and the other two on both sides work as heaters to improve the desorption performance of the sensing element to ammonia gas molecules. The graphene lines were characterized by scanning electron microscopy and Raman spectroscopy. The response and recovery time of the sensor without heating are 214 s and 222 s with a sensitivity of 0.087% ppm-1 for sensing 75 ppm ammonia gas, respectively. The experimental results prove that under the optimized heating temperature of about 70 °C the heaters successfully help implement complete desorption of residual NH₃ showing a good sensitivity and cyclic stability

Associations of plasma very-long-chain SFA and the metabolic syndrome in adults

Plasma levels of very-long-chain SFA (VLCSFA) are associated with the metabolic syndrome (MetS). However, the associations may vary by different biological activities of individual VLCSFA or population characteristics. We aimed to examine the associations of VLCSFA and MetS risk in Chinese adults. Totally, 2008 Chinese population aged 35–59 years were recruited and followed up from 2010 to 2012. Baseline MetS status and plasma fatty acids data were available for 1729 individuals without serious diseases. Among 899 initially metabolically healthy individuals, we identified 212 incident MetS during the follow-up. Logistic regression analysis was used to estimate OR and 95 % CI. Cross-sectionally, each VLCSFA was inversely associated with MetS risk; comparing with the lowest quartile, the multivariate-adjusted OR for the highest quartile were 0·18 (95 % CI 0·13, 0·25) for C20 : 0, 0·26 (95 % CI 0·18, 0·35) for C22 : 0, 0·19 (95 % CI 0·13, 0·26) for C24 : 0 and 0·16 (0·11, 0·22) for total VLCSFA (all Pfor trend<0·001). The associations remained significant after further adjusting for C16 : 0, C18 : 0, C18 : 3n-3, C22 : 6n-3, n-6 PUFA and MUFA, respectively. Based on follow-up data, C20 : 0 or C22 : 0 was also inversely associated with incident MetS risk. Among the five individual MetS components, higher levels of VLCSFA were most strongly inversely associated with elevated TAG (≥1·7 mmol/l). Plasma levels of VLCSFA were significantly and inversely associated with MetS risk and individual MetS components, especially TAG. Further studies are warranted to confirm the findings and explore underlying mechanisms

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早大学位記番号:新7063早稲田大